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LDS4
MCID: LYS017
MIFTS: 53

Loeys-Dietz Syndrome 4 (LDS4)

Categories: Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases
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Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes
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Aliases & Classifications for Loeys-Dietz Syndrome 4

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MalaCards integrated aliases for Loeys-Dietz Syndrome 4:

Name: Loeys-Dietz Syndrome 4 57 11 19 73 28 5 14 71
Lds4 57 11 73
Aneurysm, Aortic and Cerebral, with Arterial Tortuosity and Skeletal Manifestations 57 11
Aortic and Cerebral Aneurysm with Arterial Tortuosity and Skeletal Manifestations 73
Loeys-Dietz Syndrome, Type 4 38
Loeys-Dietz Syndrome Type 4 19

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
patients do not have ectopia lentis


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Skin diseases Bone diseases Eye diseases Cardiovascular diseases Immune diseases
See all MalaCards categories (disease lists)


Sources

Summaries for Loeys-Dietz Syndrome 4

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GARD: 19 Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, cervical spine malformation and/or instability), craniofacial features (widely spaced eyes, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant.

MalaCards based summary: Loeys-Dietz Syndrome 4, also known as lds4, is related to loeys-dietz syndrome 1 and marfan syndrome, and has symptoms including wrist sign and steinberg thumb sign. An important gene associated with Loeys-Dietz Syndrome 4 is TGFB2 (Transforming Growth Factor Beta 2), and among its related pathways/superpathways are ERK Signaling and Integrin Pathway. Affiliated tissues include skin, lung and artery-aorta, and related phenotypes are scoliosis and ptosis

UniProtKB/Swiss-Prot: 73 An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.

Disease Ontology: 11 A Loeys-Dietz syndrome that has material basis in heterozygous mutation in the TGFB2 gene on chromosome 1q41.

More information from OMIM: 614816 PS609192
Sources

Related Diseases for Loeys-Dietz Syndrome 4

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Diseases in the Loeys-Dietz Syndrome family:

Loeys-Dietz Syndrome 1 Loeys-Dietz Syndrome 2
Loeys-Dietz Syndrome 3 Loeys-Dietz Syndrome 4
Loeys-Dietz Syndrome 5 Loeys-Dietz Syndrome 6

Diseases related to Loeys-Dietz Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 84)
# Related Disease Score Top Affiliating Genes
1 loeys-dietz syndrome 1 30.7 TGFBR2 TGFBR1 TGFB2 SMAD3 SMAD2 FBN1
2 marfan syndrome 30.3 TGFBR2 TGFBR1 TGFB2 FBN1 ELN
3 loeys-dietz syndrome 2 30.3 TGFBR2 TGFBR1 TGFB2 SMAD3 FBN1
4 cleft palate, isolated 30.3 TGFBR2 TGFBR1 TGFB3 TGFB2 FBN1
5 contractural arachnodactyly, congenital 29.9 TGFBR2 TGFBR1 SLC2A10 FBN1 ELN
6 loeys-dietz syndrome 29.2 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
7 aortic aneurysm, familial thoracic 4 29.1 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SLC2A10
8 aortic aneurysm 29.0 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
9 loeys-dietz syndrome 3 28.9 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
10 aortic aneurysm, familial thoracic 1 28.4 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
11 orthostatic intolerance 28.3 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
12 scoliosis 10.5
13 connective tissue disease 10.5
14 hypermobile ehlers-danlos syndrome 10.5
15 isolated ectopia lentis 10.4
16 pulsating exophthalmos 10.3 TGFBR2 TGFBR1
17 ectopia lentis 2, isolated, autosomal recessive 10.2 TGFBR2 FBN1
18 multiple self-healing squamous epithelioma 10.2 TGFBR2 TGFBR1
19 ectopia lentis 1, isolated, autosomal dominant 10.2 TGFBR2 FBN1
20 hypertelorism 10.2
21 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.2
22 uvula, bifid 10.2
23 qualitative platelet defect 10.2
24 peripheral retinal degeneration 10.2
25 enterocele 10.2
26 blood platelet disease 10.2
27 cerebrovascular disease 10.2
28 retinal degeneration 10.2
29 autosomal dominant intellectual developmental disorder 19 10.2 SMAD3 SMAD2
30 camurati-engelmann disease 10.2 TGFBR2 TGFBR1 TGFB2
31 bullous keratopathy 10.2 TGFB3 TGFB2 FBN1
32 mitochondrial dna depletion syndrome 12b 10.2 TGFBR2 TGFBR1 FBN1
33 spastic paraplegia 76, autosomal recessive 10.2 TGFB3 TGFB2
34 ureteric orifice cancer 10.1 FBN1 ELN
35 tracheal stenosis 10.1 TGFB3 FBN1 ELN
36 phacogenic glaucoma 10.1 TGFB2 FBN1 ELN
37 aortitis 10.1 FBN1 ELN
38 telangiectasis 10.0 TGFBR1 FBN1 ELN
39 peyronie's disease 10.0 SMAD3 SMAD2 ELN
40 open-angle glaucoma 10.0 TGFB2 FBN1 ELN
41 glaucoma, primary open angle 10.0 TGFB2 FBN1 ELN
42 subclavian artery aneurysm 10.0 TGFBR2 TGFBR1 FBN1 ELN
43 craniosynostosis 10.0 TGFBR2 TGFBR1 TGFB3 SMAD3 FBN1
44 bladder diverticulum 10.0 SLC2A10 ELN
45 renal fibrosis 9.9 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
46 cutis laxa 9.9 SLC2A10 FBN1 ELN
47 systemic scleroderma 9.9 SMAD3 SMAD2 FBN1
48 autosomal recessive cutis laxa type i 9.9 SLC2A10 FBN1 ELN
49 intraocular pressure quantitative trait locus 9.9 TGFB2 SMAD2 FBN1 ELN
50 cutis laxa, autosomal recessive, type ib 9.9 SLC2A10 ELN

Graphical network of the top 20 diseases related to Loeys-Dietz Syndrome 4:



Diseases related to Loeys-Dietz Syndrome 4
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Symptoms & Phenotypes for Loeys-Dietz Syndrome 4

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Human phenotypes related to Loeys-Dietz Syndrome 4:

30 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 30 Very rare (1%) HP:0002650
2 ptosis 30 Very rare (1%) HP:0000508
3 hypertelorism 30 Very rare (1%) HP:0000316
4 pes planus 30 Very rare (1%) HP:0001763
5 retrognathia 30 Very rare (1%) HP:0000278
6 high, narrow palate 30 Very rare (1%) HP:0002705
7 bicuspid aortic valve 30 Very rare (1%) HP:0001647
8 aortic dissection 30 Very rare (1%) HP:0002647
9 pneumothorax 30 Very rare (1%) HP:0002107
10 joint laxity 30 Very rare (1%) HP:0001388
11 mitral valve prolapse 30 Very rare (1%) HP:0001634
12 talipes equinovarus 30 Very rare (1%) HP:0001762
13 emphysema 30 Very rare (1%) HP:0002097
14 striae distensae 30 Very rare (1%) HP:0001065
15 arachnodactyly 30 Very rare (1%) HP:0001166
16 protrusio acetabuli 30 Very rare (1%) HP:0003179
17 dural ectasia 30 Very rare (1%) HP:0100775
18 dolichocephaly 30 Very rare (1%) HP:0000268
19 downslanted palpebral fissures 30 Very rare (1%) HP:0000494
20 spondylolisthesis 30 Very rare (1%) HP:0003302
21 aortic tortuosity 30 Very rare (1%) HP:0006687
22 flat cornea 30 Very rare (1%) HP:0007720
23 joint hyperflexibility 30 Very rare (1%) HP:0005692
24 bruising susceptibility 30 Very rare (1%) HP:0000978
25 tall stature 30 Very rare (1%) HP:0000098
26 hyperextensible skin 30 Very rare (1%) HP:0000974
27 bifid uvula 30 Very rare (1%) HP:0000193
28 aortic root aneurysm 30 Very rare (1%) HP:0002616
29 torticollis 30 Very rare (1%) HP:0000473
30 arterial tortuosity 30 Very rare (1%) HP:0005116
31 ascending tubular aorta aneurysm 30 Very rare (1%) HP:0004970
32 chronic pain 30 Very rare (1%) HP:0012532
33 broad uvula 30 Very rare (1%) HP:0010809
34 abnormal sternum morphology 30 Very rare (1%) HP:0000766
35 recurrent thrombophlebitis 30 Very rare (1%) HP:0004419
36 inguinal hernia 30 HP:0000023
37 eosinophilic infiltration of the esophagus 30 HP:0410151

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Skeletal Spine:
scoliosis
spondylolisthesis (rare)

Genitourinary External Genitalia Female:
inguinal hernia

Cardiovascular Vascular:
aortic dissection
aortic root aneurysm
arterial tortuosity
cerebrovascular aneurysm (in some patients)
fusiform dilation and tortuosity of cerebrovascular arteries

Skeletal Hands:
arachnodactyly
steinberg thumb sign

Skeletal:
joint hyperflexibility
tall stature

Skin Nails Hair Skin:
easy bruising
skin striae

Head And Neck Mouth:
high-arched palate
broad or bifid uvula (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Skeletal Pelvis:
protrusio acetabularis

Genitourinary External Genitalia Male:
inguinal hernia

Head And Neck Face:
retrognathia

Cardiovascular Heart:
mitral valve prolapse
bicuspid aortic valve (rare)

Neurologic Central Nervous System:
dural ectasia

Skeletal Limbs:
wrist sign

Skeletal Feet:
flat feet
club feet (in some patients)

Head And Neck Eyes:
hypertelorism (in some patients)
downslanting palpebral fissures (in some patients)

Respiratory Lung:
emphysema (rare)
pneumothorax (rare)

Clinical features from OMIM®:

614816 (Updated 08-Dec-2022)

UMLS symptoms related to Loeys-Dietz Syndrome 4:


wrist sign; steinberg thumb sign

GenomeRNAi Phenotypes related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

25 (show all 34)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.92 SMAD2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.92 SMAD2 TGFB2 TGFBR1 TGFBR2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.92 TGFB2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.92 TGFBR2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.92 TGFBR2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-138 9.92 TGFB2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-14 9.92 TGFB2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.92 TGFBR1 TGFBR2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-162 9.92 TGFBR2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-165 9.92 TGFBR2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.92 TGFBR1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-172 9.92 SMAD2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-174 9.92 SMAD2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-186 9.92 TGFBR2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.92 TGFBR2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.92 TGFB2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-200 9.92 TGFBR1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-203 9.92 SMAD2
19 Increased shRNA abundance (Z-score > 2) GR00366-A-205 9.92 SMAD2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.92 TGFB2
21 Increased shRNA abundance (Z-score > 2) GR00366-A-22 9.92 TGFBR1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-25 9.92 SMAD2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-37 9.92 TGFBR1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-39 9.92 TGFBR2
25 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.92 TGFB2
26 Increased shRNA abundance (Z-score > 2) GR00366-A-48 9.92 TGFBR2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-59 9.92 TGFB2
28 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.92 TGFB2 TGFBR1 TGFBR2
29 Increased shRNA abundance (Z-score > 2) GR00366-A-7 9.92 TGFBR2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-72 9.92 TGFB2
31 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.92 TGFB2
32 Increased shRNA abundance (Z-score > 2) GR00366-A-77 9.92 TGFBR1
33 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.92 TGFBR1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.92 TGFBR1

MGI Mouse Phenotypes related to Loeys-Dietz Syndrome 4:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.97 FBN1 NDUFA9 SMAD2 SMAD3 TGFB2 TGFB3
2 cardiovascular system MP:0005385 9.9 ELN FBN1 MYH11 PPFIA2 SLC2A10 SMAD2
3 digestive/alimentary MP:0005381 9.87 MYH11 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1
4 craniofacial MP:0005382 9.8 FBN1 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1
5 respiratory system MP:0005388 9.61 ELN FBN1 MYH11 SLC2A10 SMAD2 TGFB2
6 skeleton MP:0005390 9.28 B3GAT3 ELN FBN1 SMAD2 SMAD3 TGFB2
Sources

Drugs & Therapeutics for Loeys-Dietz Syndrome 4

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Search Clinical Trials, NIH Clinical Center for Loeys-Dietz Syndrome 4

Sources

Genetic Tests for Loeys-Dietz Syndrome 4

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Genetic tests related to Loeys-Dietz Syndrome 4:

# Genetic test Affiliating Genes
1 Loeys-Dietz Syndrome 4 28 TGFB2
Sources

Anatomical Context for Loeys-Dietz Syndrome 4

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Organs/tissues related to Loeys-Dietz Syndrome 4:

MalaCards : Skin, Lung
ODiseA: Artery-Aorta, Artery-Coronary, Artery, Respiratory System-Lung, Respiratory System
Sources

Publications for Loeys-Dietz Syndrome 4

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Articles related to Loeys-Dietz Syndrome 4:

(show all 27)
# Title Authors PMID Year
1
Whole exome sequencing for the identification of a new mutation in TGFB2 involved in a familial case of non-syndromic aortic disease. 57 5
25046559 2014
2
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. 57 5
22772371 2012
3
Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. 57 5
22772368 2012
4
Corneal thinning and cornea guttata in patients with mutations in TGFB2. 62 5
32307099 2020
5
Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders. 5
34008892 2021
6
Genetic diversity and pathogenic variants as possible predictors of severity in a French sample of nonsyndromic heritable thoracic aortic aneurysms and dissections (nshTAAD). 5
30739908 2019
7
Testing patterns for genetically triggered aortic and arterial aneurysms and dissections at an academic center. 5
29510914 2018
8
A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3. 5
29392890 2018
9
High diagnostic yield of clinically unidentifiable syndromic growth disorders by targeted exome sequencing. 5
28425089 2017
10
4.7 Mb deletion encompassing TGFB2 associated with features of Loeys-Dietz syndrome and osteoporosis in adulthood. 5
28544325 2017
11
Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing. 5
26854089 2016
12
Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting. 5
26188975 2015
13
Exome sequencing identifies a novel heterozygous TGFB3 mutation in a disorder overlapping with Marfan and Loeys-Dietz syndrome. 5
26184463 2015
14
Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections. 5
25835445 2015
15
Gene panel sequencing in heritable thoracic aortic disorders and related entities - results of comprehensive testing in a cohort of 264 patients. 5
25644172 2015
16
De novo mutation of the latency-associated peptide domain of TGFB3 in a patient with overgrowth and Loeys-Dietz syndrome features. 5
24798638 2014
17
Thoracic aortic-aneurysm and dissection in association with significant mitral valve disease caused by mutations in TGFB2. 5
23102774 2013
18
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
19
[Comparison of results between the Robinson method of drainage and marsupialization]. 5
2618446 1989
20
[A pedigree study of Loeys-Dietz syndrome type 4 with skeletal deformity related to a novel TGFβ2 mutation]. 62
35488607 2022
21
Differential Diagnosis between Marfan Syndrome and Loeys-Dietz Syndrome Type 4: A Novel Chromosomal Deletion Covering TGFB2. 62
34680857 2021
22
Prenatal ultrasound features of Loeys-Dietz syndrome Type 4. 62
32119163 2021
23
Ectopia lentis in Loeys-Dietz syndrome type 4. 62
32462795 2020
24
Phenotypic variability and diffuse arterial lesions in a family with Loeys-Dietz syndrome type 4. 62
27440102 2017
25
Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation. 62
25163805 2014
26
Loeys-Dietz syndrome type 4, caused by chromothripsis, involving the TGFB2 gene. 62
24440784 2014
27
Diagnostic yield in adults screened at the Marfan outpatient clinic using the 1996 and 2010 Ghent nosologies. 62
22461464 2012
Sources

Variations for Loeys-Dietz Syndrome 4

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ClinVar genetic disease variations for Loeys-Dietz Syndrome 4:

5 (show top 50) (show all 614)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TGFB2 NM_003238.6(TGFB2):c.687C>A (p.Cys229Ter) SNV Pathogenic
 37088 rs398122885 GRCh37: 1:218607723-218607723
GRCh38: 1:218434381-218434381
2 TGFB2 NM_001135599.4:c.595_1245del DEL Pathogenic
 620591 GRCh37:
GRCh38:
3 TGFB3 NC_000014.9:g.(?_75958692)_(75980923_?)del DEL Pathogenic
 832288 GRCh37: 14:76425035-76447266
GRCh38:
4 overlap with 4 genes DEL Pathogenic
 1199382 GRCh37: 1:217589671-219026274
GRCh38:
5 overlap with 10 genes DEL Pathogenic
 1199383 GRCh37: 1:216243817-220231236
GRCh38:
6 overlap with 6 genes DEL Pathogenic
 1199384 GRCh37: 1:217219510-219385296
GRCh38:
7 overlap with 2 genes DEL Pathogenic
 1199385 GRCh37: 1:218238773-219024035
GRCh38:
8 overlap with 29 genes DEL Pathogenic
 1199386 GRCh37: 1:215199578-223035427
GRCh38:
9 TGFB3 NM_003239.5(TGFB3):c.996G>A (p.Trp332Ter) SNV Pathogenic
 1369504 GRCh37: 14:76427350-76427350
GRCh38: 14:75961007-75961007
10 TGFB3 NM_003239.5(TGFB3):c.723del (p.Asn241fs) DEL Pathogenic
 1392107 GRCh37: 14:76431962-76431962
GRCh38: 14:75965619-75965619
11 TGFB2 NM_003238.6(TGFB2):c.329_330dup (p.Phe111fs) DUP Pathogenic
 1393330 GRCh37: 1:218520370-218520371
GRCh38: 1:218347028-218347029
12 TGFB2 NM_003238.6(TGFB2):c.868dup (p.Arg290fs) DUP Pathogenic
 1458546 GRCh37: 1:218609424-218609425
GRCh38: 1:218436082-218436083
13 TGFB3 NC_000014.8:g.(?_76425530)_(76447236_?)del DEL Pathogenic
 1459322 GRCh37: 14:76425530-76447236
GRCh38:
14 TGFB3 NM_003239.5(TGFB3):c.436del (p.Leu146fs) DEL Pathogenic
 1453884 GRCh37: 14:76437978-76437978
GRCh38: 14:75971635-75971635
15 TGFB2 NM_003238.6(TGFB2):c.912_930del (p.Asp305fs) DEL Pathogenic
 1299635 GRCh37: 1:218609463-218609481
GRCh38: 1:218436121-218436139
16 TGFB3 NM_003239.5(TGFB3):c.621del (p.Val208fs) DEL Pathogenic
 1215028 GRCh37: 14:76437494-76437494
GRCh38: 14:75971151-75971151
17 TGFB2 NC_000001.10:g.(?_218520044)_(218607810_?)del DEL Pathogenic
 1455704 GRCh37: 1:218520044-218607810
GRCh38:
18 TGFB2 NM_003238.6(TGFB2):c.196del (p.Glu66fs) DEL Pathogenic
 1452939 rs863223794 GRCh37: 1:218520238-218520238
GRCh38: 1:218346896-218346896
19 TGFB2 NM_003238.6(TGFB2):c.145A>T (p.Lys49Ter) SNV Pathogenic
 1451388 GRCh37: 1:218520188-218520188
GRCh38: 1:218346846-218346846
20 TGFB3 NM_003239.5(TGFB3):c.355del (p.Glu119fs) DEL Pathogenic
 1451952 GRCh37: 14:76438059-76438059
GRCh38: 14:75971716-75971716
21 TGFB2 NM_003238.6(TGFB2):c.171T>A (p.Tyr57Ter) SNV Pathogenic
 1452940 GRCh37: 1:218520214-218520214
GRCh38: 1:218346872-218346872
22 TGFB2 NM_003238.6(TGFB2):c.456dup (p.Arg153fs) DUP Pathogenic
 1351917 GRCh37: 1:218578617-218578618
GRCh38: 1:218405275-218405276
23 TGFB3 NM_003239.5(TGFB3):c.170dup (p.Pro57_Glu58insTer) DUP Pathogenic
 1075580 GRCh37: 14:76447066-76447067
GRCh38: 14:75980723-75980724
24 TGFB3 NM_003239.5(TGFB3):c.883_884del (p.Gly295fs) DEL Pathogenic
 410268 rs1060502826 GRCh37: 14:76429701-76429702
GRCh38: 14:75963358-75963359
25 TGFB3 NM_003239.5(TGFB3):c.989G>A (p.Trp330Ter) SNV Pathogenic
 477652 rs1555360222 GRCh37: 14:76427357-76427357
GRCh38: 14:75961014-75961014
26 TGFB3 NM_003239.5(TGFB3):c.899G>A (p.Arg300Gln) SNV Pathogenic
 143945 rs587777617 GRCh37: 14:76429686-76429686
GRCh38: 14:75963343-75963343
27 TGFB3 NM_003239.5(TGFB3):c.990G>A (p.Trp330Ter) SNV Pathogenic
 1072149 GRCh37: 14:76427356-76427356
GRCh38: 14:75961013-75961013
28 TGFB2 NC_000001.10:g.(?_218520044)_(218614704_?)del DEL Pathogenic
 1458168 GRCh37: 1:218520044-218614704
GRCh38:
29 overlap with 21 genes DEL Pathogenic
 224870 GRCh37: 1:215588712-222145072
GRCh38:
30 overlap with 8 genes DEL Pathogenic
 224871 GRCh37: 1:216672181-220202575
GRCh38:
31 TGFB2 NM_003238.6(TGFB2):c.895C>T (p.Arg299Trp) SNV Pathogenic
 213845 rs863223792 GRCh37: 1:218609452-218609452
GRCh38: 1:218436110-218436110
32 TGFB2 NM_003238.6(TGFB2):c.297C>A (p.Tyr99Ter) SNV Pathogenic
 224874 rs760759052 GRCh37: 1:218520340-218520340
GRCh38: 1:218346998-218346998
33 TGFB2 NM_003238.6(TGFB2):c.1013C>A (p.Pro338His) SNV Pathogenic
 37085 rs387907278 GRCh37: 1:218610765-218610765
GRCh38: 1:218437423-218437423
34 TGFB2 NM_003238.6(TGFB2):c.1022_1026del (p.Tyr341fs) DEL Pathogenic
 224873 rs398122884 GRCh37: 1:218610773-218610777
GRCh38: 1:218437431-218437435
35 TGFB3 NM_003239.5(TGFB3):c.1034C>G (p.Ser345Ter) SNV Pathogenic
 410269 rs1060502827 GRCh37: 14:76427312-76427312
GRCh38: 14:75960969-75960969
36 TGFB3 NM_003239.5(TGFB3):c.898C>T (p.Arg300Trp) SNV Pathogenic
 203490 rs796051885 GRCh37: 14:76429687-76429687
GRCh38: 14:75963344-75963344
37 TGFB3 NM_003239.5(TGFB3):c.973C>T (p.Arg325Ter) SNV Pathogenic
 477651 rs1555360229 GRCh37: 14:76427373-76427373
GRCh38: 14:75961030-75961030
38 TGFB2 NM_003238.6(TGFB2):c.896G>A (p.Arg299Gln) SNV Pathogenic
 381708 rs1057521150 GRCh37: 1:218609453-218609453
GRCh38: 1:218436111-218436111
39 TGFB3 NM_003239.5(TGFB3):c.442C>T (p.Arg148Ter) SNV Pathogenic
 390113 rs1057523647 GRCh37: 14:76437972-76437972
GRCh38: 14:75971629-75971629
40 TGFB3 NM_003239.5(TGFB3):c.109A>T (p.Lys37Ter) SNV Pathogenic
 862476 rs2035418540 GRCh37: 14:76447128-76447128
GRCh38: 14:75980785-75980785
41 TGFB2 NM_003238.6(TGFB2):c.544C>T (p.Gln182Ter) SNV Pathogenic
 180536 rs730880221 GRCh37: 1:218607457-218607457
GRCh38: 1:218434115-218434115
42 TGFB2 NM_003238.6(TGFB2):c.583G>T (p.Glu195Ter) SNV Pathogenic
 213841 rs863223790 GRCh37: 1:218607496-218607496
GRCh38: 1:218434154-218434154
43 TGFB2 NM_003238.6(TGFB2):c.391C>T (p.Arg131Ter) SNV Pathogenic
 222832 rs869025531 GRCh37: 1:218578555-218578555
GRCh38: 1:218405213-218405213
44 TGFB2 NM_003238.6(TGFB2):c.904C>A (p.Arg302Ser) SNV Pathogenic
 239515 rs869312903 GRCh37: 1:218609461-218609461
GRCh38: 1:218436119-218436119
45 TGFB2 NM_003238.6(TGFB2):c.252dup (p.Arg85fs) DUP Pathogenic
 408427 rs1553292112 GRCh37: 1:218520293-218520294
GRCh38: 1:218346951-218346952
46 TGFB2 NM_003238.6(TGFB2):c.821dup (p.Asn274fs) DUP Pathogenic
 213849 rs863223796 GRCh37: 1:218609370-218609371
GRCh38: 1:218436028-218436029
47 TGFB2 NM_003238.6(TGFB2):c.905G>A (p.Arg302His) SNV Pathogenic
 440982 rs1553303213 GRCh37: 1:218609462-218609462
GRCh38: 1:218436120-218436120
48 TGFB2 NM_003238.6(TGFB2):c.892_901del (p.Arg298fs) DEL Pathogenic
 459270 rs1553303203 GRCh37: 1:218609449-218609458
GRCh38: 1:218436107-218436116
49 TGFB2 NC_000001.11:g.(?_218346682)_(218441382_?)del DEL Pathogenic
 528890 GRCh37: 1:218520024-218614724
GRCh38: 1:218346682-218441382
50 TGFB2 NM_003238.6(TGFB2):c.990dup (p.Gly331fs) DUP Pathogenic
 643407 rs1571904218 GRCh37: 1:218610741-218610742
GRCh38: 1:218437399-218437400

UniProtKB/Swiss-Prot genetic disease variations for Loeys-Dietz Syndrome 4:

73
# Symbol AA change Variation ID SNP ID
1 TGFB2 p.Arg299Trp VAR_068932 rs863223792
2 TGFB2 p.Arg302Cys VAR_068933 rs869312903
3 TGFB2 p.Pro338His VAR_068934 rs387907278

Sources

Expression for Loeys-Dietz Syndrome 4

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Search GEO for disease gene expression data for Loeys-Dietz Syndrome 4.
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Pathways for Loeys-Dietz Syndrome 4

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Pathways related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 49)
# Super pathways Score Top Affiliating Genes
1
ERK Signaling 64
Show member pathways
 13.8 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
2
Integrin Pathway 64
Show member pathways
 13.37 ELN FBN1 MYH11 TGFB2 TGFB3 TGFBR1
3
PAK Pathway 64
Show member pathways
 13.28 MYH11 SLC2A10 SMAD3 TGFB2 TGFB3 TGFBR1
4
Sertoli-Sertoli Cell Junction Dynamics 64
Show member pathways
 12.88 TGFBR2 TGFBR1 TGFB3 TGFB2 MYH11
5
Toll-like receptor signaling pathway 74
Show member pathways
 12.85 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
6
Endometrial cancer 74
Show member pathways
 12.72 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
7
Human Embryonic Stem Cell Pluripotency 64
Show member pathways
 12.53 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
8
Cell cycle Regulation of G1/S transition (part 1) 22
Show member pathways
 12.43 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
9
Signaling by TGFB family members 66
Show member pathways
 12.4 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
10
MAPK signaling pathway 74
12.37 TGFBR2 TGFBR1 TGFB3 TGFB2
11
Wnt / Hedgehog / Notch 3
12.27 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
12
Colorectal Cancer Metastasis 64
12.25 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1 TGFBR2
13
Cell cycle 74
Show member pathways
 12.24 TGFB3 TGFB2 SMAD3 SMAD2
14
Epithelial to mesenchymal transition in colorectal cancer 74
12.23 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
15
Neuroinflammation and glutamatergic signaling 74
12.12 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
16
TGF-beta receptor signaling in skeletal dysplasias 74
Show member pathways
 12.05 FBN1 SMAD2 SMAD3 TGFBR1 TGFBR2
17
GDNF signaling 74
12 TGFBR1 SMAD3 SMAD2
18
Cytokine production by Th17 cells in CF (Mouse model) 22
Show member pathways
 11.9 SMAD2 SMAD3 TGFBR1 TGFBR2
19
TGF-beta Signaling Pathways 65
11.86 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
20
Burn wound healing 74
11.85 TGFB3 TGFB2 SMAD3 FBN1 ELN
21
Elastic fibre formation 66
Show member pathways
 11.84 TGFB3 TGFB2 FBN1 ELN
22
Overlap between signal transduction pathways contributing to LMNA laminopathies 74
Show member pathways
 11.83 TGFB2 SMAD3 SMAD2
23
Angiogenesis (CST) 3
11.81 TGFBR1 TGFB3 TGFB2
24
Development_TGF-beta receptor signaling 22
11.78 TGFBR2 TGFBR1 SMAD3 SMAD2
25
Transcription_P53 signaling pathway 22
11.78 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
26
Th17 Differentiation 65
Show member pathways
 11.76 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1 TGFBR2
27
IL-2 Gene Expression in Activated and Quiescent T-Cells 64
Show member pathways
 11.6 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
28
TGF-beta receptor signaling 61
11.57 SMAD2 SMAD3 TGFB3 TGFBR1 TGFBR2
29
Cell adhesion_Plasmin signaling 22
11.53 TGFBR2 TGFBR1 TGFB2
30
Interactions between immune cells and microRNAs in tumor microenvironment 74
11.52 TGFBR2 TGFB3 TGFB2
31
Envelope proteins and their potential roles in EDMD physiopathology 74
11.39 TGFB3 SMAD3 SMAD2
32
SMAD2/3 Phosphorylation Motif Mutants in Cancer 66
Show member pathways
 11.32 TGFBR2 TGFBR1 SMAD3 SMAD2
33
Neovascularisation processes 74
11.3 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
34
Angiotensin II receptor type 1 pathway 74
11.27 TGFBR2 TGFBR1 SMAD3
35
ALK1 signaling events 61
Show member pathways
 11.22 TGFBR2 TGFBR1 TGFB3
36
Progeria-associated lipodystrophy 74
Show member pathways
 11.16 SMAD3 SMAD2 FBN1
37
NRP1-triggered signaling pathways in pancreatic cancer 74
11.16 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
38
TGF-beta receptor signaling activates SMADs 66
Show member pathways
 11.16 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
39
Glypican 1 network 61
11.12 TGFBR2 TGFBR1 TGFB3 SMAD2
40
Extracellular vesicle-mediated signaling in recipient cells 74
11.1 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
41
IL-4 Signaling and its Primary Biological Effects in Different Immune Cell Types 65
11.06 TGFBR2 TGFBR1 TGFB3 TGFB2
42
Regucalcin in proximal tubule epithelial kidney cells 74
11.05 TGFBR1 SMAD2
43
Canonical and non-canonical TGF-B signaling 74
11.04 TGFBR2 TGFBR1 SMAD3 SMAD2
44
Hypothesized pathways in pathogenesis of cardiovascular disease 74
10.95 TGFBR2 TGFBR1 SMAD3 SMAD2 FBN1
45
Beta5 beta6 beta7 and beta8 integrin cell surface interactions 61
10.93 TGFBR1 FBN1
46
TGF-beta signaling in thyroid cells for epithelial-mesenchymal transition 74
10.84 SMAD3 SMAD2
47
Regulation of cytoplasmic and nuclear SMAD2/3 signaling 61
10.81 SMAD3 SMAD2
48
IL-9 Signaling and its Primary Biological Effects in Different Immune Cell Types 65
10.77 TGFB3 TGFB2
49
SMAD2/3 MH2 Domain Mutants in Cancer 66
Show member pathways
 10.63 SMAD3 SMAD2
Sources

GO Terms for Loeys-Dietz Syndrome 4

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Cellular components related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heteromeric SMAD protein complex GO:0071144 9.46 SMAD3 SMAD2
2 SMAD protein complex GO:0071141 9.26 SMAD3 SMAD2
3 transforming growth factor beta ligand-receptor complex GO:0070021 8.92 TGFBR2 TGFBR1

Biological processes related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 35)
# Name GO ID Score Top Affiliating Genes
1 in utero embryonic development GO:0001701 10.27 TGFBR2 TGFBR1 TGFB3 SMAD3 SMAD2
2 response to hypoxia GO:0001666 10.25 TGFBR2 TGFB3 TGFB2 SMAD3
3 heart development GO:0007507 10.23 FBN1 SMAD2 TGFB2 TGFBR1 TGFBR2
4 skeletal system development GO:0001501 10.16 TGFBR1 TGFB2 SMAD3 FBN1
5 cellular response to transforming growth factor beta stimulus GO:0071560 10.14 TGFBR1 SMAD3 FBN1
6 positive regulation of stress fiber assembly GO:0051496 10.11 TGFBR1 TGFB3 SMAD3
7 SMAD protein signal transduction GO:0060395 10.1 TGFB3 TGFB2 SMAD3 SMAD2
8 ventricular septum morphogenesis GO:0060412 10.08 TGFBR2 TGFBR1 TGFB2
9 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 10.06 TGFBR2 TGFBR1 TGFB3 TGFB2
10 BMP signaling pathway GO:0030509 10.02 SMAD2 SMAD3 TGFB2 TGFB3
11 cell-cell junction organization GO:0045216 10.01 TGFB3 TGFB2 SMAD3
12 embryonic cranial skeleton morphogenesis GO:0048701 10.01 TGFBR2 TGFBR1 SMAD3 SMAD2
13 gastrulation GO:0007369 9.98 TGFBR2 SMAD3 SMAD2
14 nodal signaling pathway GO:0038092 9.96 SMAD2 SMAD3
15 pericardium development GO:0060039 9.96 SMAD3 SMAD2
16 embryonic foregut morphogenesis GO:0048617 9.96 SMAD3 SMAD2
17 membranous septum morphogenesis GO:0003149 9.95 TGFBR2 TGFB2
18 pathway-restricted SMAD protein phosphorylation GO:0060389 9.95 TGFB2 TGFBR1 TGFBR2
19 salivary gland morphogenesis GO:0007435 9.94 TGFB2 TGFB3
20 SMAD protein complex assembly GO:0007183 9.93 SMAD3 SMAD2
21 common-partner SMAD protein phosphorylation GO:0007182 9.93 TGFBR2 SMAD2
22 transforming growth factor beta receptor signaling pathway GO:0007179 9.93 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1 TGFBR2
23 activin receptor signaling pathway GO:0032924 9.92 TGFBR2 TGFBR1 SMAD3 SMAD2
24 endocardial cushion fusion GO:0003274 9.91 TGFB2 TGFBR2
25 response to cholesterol GO:0070723 9.91 TGFBR2 TGFBR1 SMAD2
26 regulation of binding GO:0051098 9.9 SMAD3 SMAD2
27 regulation of transforming growth factor beta2 production GO:0032909 9.89 TGFB2 SMAD3
28 positive regulation of tight junction disassembly GO:1905075 9.86 TGFBR1 TGFB3
29 secondary palate development GO:0062009 9.86 TGFBR2 TGFB3 TGFB2 SMAD2
30 positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation GO:1905007 9.85 TGFB2 TGFBR1 TGFBR2
31 paraxial mesoderm morphogenesis GO:0048340 9.83 SMAD3 SMAD2
32 uterine wall breakdown GO:0042704 9.81 TGFB3 TGFB2
33 wound healing GO:0042060 9.73 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
34 regulation of multicellular organismal process GO:0051239 9.62 TGFBR2 TGFBR1
35 positive regulation of epithelial to mesenchymal transition GO:0010718 9.4 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2

Molecular functions related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transforming growth factor beta binding GO:0050431 9.88 TGFBR2 TGFBR1 TGFB3
2 SMAD binding GO:0046332 9.87 SMAD2 SMAD3 TGFBR1 TGFBR2
3 I-SMAD binding GO:0070411 9.85 TGFBR1 SMAD3 SMAD2
4 extracellular matrix constituent conferring elasticity GO:0030023 9.76 FBN1 ELN
5 transforming growth factor beta receptor activity GO:0005024 9.73 TGFBR2 TGFBR1
6 type I transforming growth factor beta receptor binding GO:0034713 9.73 TGFBR2 TGFB3 SMAD2
7 transmembrane receptor protein serine/threonine kinase activity GO:0004675 9.65 TGFBR2 TGFBR1
8 type II transforming growth factor beta receptor binding GO:0005114 9.63 TGFBR1 TGFB3 TGFB2
9 type III transforming growth factor beta receptor binding GO:0034714 9.35 TGFBR2 TGFB3 TGFB2
10 transforming growth factor beta receptor binding GO:0005160 9.17 TGFB3 TGFB2 SMAD3 SMAD2
Sources

Sources for Loeys-Dietz Syndrome 4

About this section
2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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